共查询到20条相似文献,搜索用时 31 毫秒
1.
Several spectrophotometric and HPLC methods are presented for the determination of fenofibrate, vinpocetine and their hydrolysis products. The resolution of either fenofibrate or vinpocetine and their hydrolysis products has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression (PCR) applied to UV spectra; and graphical spectrophotometric methods as first derivative of ratio spectra (1DD) or first (1D) and second (2D) derivative spectrophotometry for vinpocetine and fenofibrate, respectively. In addition HPLC methods were developed using ODS column with mobile phase consisting of acetonitrile-water (80:20, v/v, pH 4) with UV detection at 287 nm for fenofibrate and a mobile phase consisting of acetonitrile-10 mM KH2PO4, containing 0.1% diethylamine (60:40, v/v, pH 4.6) with UV detection at 270 nm for vinpocetine. The proposed methods were successfully applied for the determination of each drug and its hydrolysis product in laboratory-prepared mixture and pharmaceutical preparation. The proposed HPLC and derivative spectrophotometric methods were used to investigate the kinetics of acidic and alkaline hydrolytic processes of each drug. The pH-rate profile of hydrolysis of each drug in Britton-Robinson buffer solutions was studied. 相似文献
2.
el-Gindy A el-Yazby F Mostafa A Maher MM 《Journal of pharmaceutical and biomedical analysis》2004,35(4):703-713
Three methods are presented for the simultaneous determination of cyproheptadine hydrochloride (CP), thiamine hydrochloride (B1), riboflavin-5-phosphate sodium dihydrate (B2), nicotinamide (B3), pyridoxine hydrochloride (B6), and sorbic acid (SO). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase, RP 18 column. Elution was carried out with 0.1% methanolic hexane sulphonic acid sodium salt (solvent A) and 0.01 M phosphate buffer containing 0.1% hexane sulphonic acid sodium salt, adjusted to an apparent pH of 2.7 (solvent B). Gradient HPLC was used with the solvent ratio changed from 20:80 to 70:30 (over 9 min), then to 80:20 (over 11 min) for solvent A:B, respectively. Quantitation was achieved with UV detection at 220 and 288 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS). These approaches were successfully applied to quantify each drug in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 250-290 nm with the intervals Deltalambda = 0.4 nm at 100 wavelengths. The chemometric methods do not require any separation step. The three methods were successfully applied to a pharmaceutical formulation and the results were compared with each other. 相似文献
3.
Three methods are developed for the simultaneous determination of theophylline anhydrous (TH), guaiphenesin (GP), diphenhydramine hydrochloride (DP), methylparaben (MP), propylparaben (PP) and sodium benzoate (BZ) in pharmaceutical syrup. The chromatographic method depends on a high performance liquid chromatographic separation on a reversed-phase C(18) column at ambient temperature with mobile phase consisting of 25 mM KH2PO4, pH 3.2-acetonitrile (60:40, v/v). Quantitation was achieved with UV detection at 222 nm based on peak area. The other two chemometric methods applied were partial least squares (PLS-1) and principal component regression (PCR). These approaches were successfully applied to quantify the six components in the studied mixture using information included in the UV absorption spectra of appropriate solutions in the wavelength range of 220-270 nm with Deltalambda=0.4 nm. The calibration PLS-1 and PCR models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over synthetic and pharmaceutical preparation. The results of PLS-1 and PCR methods were compared with the HPLC method and a good agreement was found. 相似文献
4.
El-Gindy A 《Il Farmaco; edizione pratica》2005,60(9):745-753
Three methods are developed for the simultaneous determination of diprophylline (DP), phenobarbitone (PH) and papaverine hydrochloride (PP). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase C18 column with a mobile phase consisting of 0.02 M potassium dihydrogen phosphate, pH 3.5--acetonitrile (55:45 v/v). Quantitation was achieved with UV detection at 210 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS-1). These approaches were successfully applied to quantify the three drugs in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 215-245 nm with the intervals Delta lambda = 0.2 nm. The calibration PCR and PLS-1 models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over laboratory-prepared mixtures and pharmaceutical preparations. The PCR and PLS-1 methods require neither any separation step, nor any priori graphical treatment of the overlapping spectra of the three drugs in a mixture. The results of PCR and PLS-1 methods were compared with HPLC method obtained in pharmaceutical formulation and a good agreement was found. 相似文献
5.
Three methods are presented for the determination of Nicergoline in presence of its hydrolysis-induced degradation product. The first method was based on measurement of the first derivative of ratio spectra amplitude of Nicergoline at 291 nm. The second method was based on separation of Nicergoline from its degradation product followed by densitometric measurement of the spots at 287 nm. The separation was carried out on HPTLC silica gel F(254) plates, using methanol-ethyl acetate-glacial acetic acid (5:7:3, v/v/v) as mobile phase. The third method was based on high performance liquid chromatographic (HPLC) separation and determination of Nicergoline from its degradation product on a reversed phase, nucloesil C(18) column using a mobile phase of methanol-water-glacial acetic acid (80:20:0.1, v/v/v) with UV detection at 280 nm. Chlorpromazine hydrochloride was used as internal standard. Laboratory prepared mixtures containing different percentages of the degradation product were analysed by the proposed methods and satisfactory results were obtained. These methods have been successfully applied to the analysis of Nicergoline in Sermion tablets. The validities of these methods were ascertained by applying standard addition technique, the mean percentage recovery +/- R.S.D.% was found to be 99.47 +/- 0.752, 100.01 +/- 0.940, 99.75 +/- 0.740 for the first derivative of ratio spectra method, the HPTLC method and the HPLC method, respectively. The proposed methods were statistically compared with the manufacturer's HPLC method of analysis of Nicergoline and no significant difference was found with respect to both precision and accuracy. They have the advantage of being stability indicating. Therefore, they can be used for routine analysis of the drug in quality control laboratories. 相似文献
6.
Simultaneous determination of valsartan and hydrochlorothiazide in tablets by first-derivative ultraviolet spectrophotometry and LC 总被引:1,自引:0,他引:1
Satana E Altinay S Göğer NG Ozkan SA Sentürk Z 《Journal of pharmaceutical and biomedical analysis》2001,25(5-6):1009-1013
First-derivative ultraviolet spectrophotometry and high-performance liquid chromatography (HPLC) were used to determine valsartan and hydrochlorothiazide simultaneously in combined pharmaceutical dosage forms. The derivative procedure was based on the linear relationship between the drug concentration and the first derivative amplitudes at 270.6 and 335 nm for valsartan and hydrochlorothiazide, respectively. The calibration graphs were linear in the range of 12.0–36.1 μg ml−1 for valsartan and 4.0–12.1 μg ml−1 for hydrochlorothiazide. Furthermore, a high- performance liquid chromatographic procedure with ultraviolet detection at 225 nm was developed for a comparison method. For the HPLC procedure, a reversed phase column with a mobile phase of 0.02 M phosphate buffer (pH 3.2)-acetonitrile (55: 45; v/v), was used to separate for valsartan and hydrochlorothiazide. The plot of peak area ratio of each drug to the internal standard versus the respective concentrations of valsartan and hydrochlorothiazide were found to be linear in the range of 0.06–1.8 and 0.07–0.5 μg ml−1, respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and commercial tablets. 相似文献
7.
Comparison of spectrophotometric and an LC method for the determination perindopril and indapamide in pharmaceutical formulations. 总被引:1,自引:0,他引:1
N Erk 《Journal of pharmaceutical and biomedical analysis》2001,26(1):43-52
A new sensitive, simple, rapid and precise reversed-phase high performance liquid chromatographic (HPLC) and two spectrophotometric methods have been developed for resolving binary mixture of perindopril and indapamide in the pharmaceutical dosage forms. The first method is based on HPLC on a reversed-phase column using a mobile phase of phosphate buffer pH 2.4 and acetonitrile (7:3 v/v) was used. Linearity range for perindopril and indapamide was 5.0-70.0 and 8.0-35.0 microg ml(-1). In the second method, the first derivative spectrophotometry with a zero-crossing technique of measurement is used for the simultaneous quantitative determination of perindopril and indapamide in binary mixtures without previous separation step. Linear calibration graphs of first derivative values at 225.7 and 255.4 nm for perindopril and indapamide, respectively. The third method is based on ratio derivative spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 226.5 and at 255.3 nm were selected to determine perindopril and indapamide in the binary mixture. All the proposed methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the pharmaceutical dosage forms containing the above-mentioned drug combination without any interference by the excipients. 相似文献
8.
Three methods are developed for the determination of two multicomponent mixtures containing guaiphenesine (GU) with salbutamol sulfate (SL), methylparaben (MP) and propylparaben (PP) [mixture 1]; and acephylline piperazine (AC) with bromhexine hydrochloride (BX), methylparaben (MP) and propylparaben (PP) [mixture 2]. The resolution of the two multicomponent mixtures has been accomplished by using numerical spectrophotometric methods such as partial least squares (PLS-1) and principal component regression (PCR) applied to UV absorption spectra of the two mixtures. In addition HPLC method was developed using a RP 18 column at ambient temperature with mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 4.3 (60:40, v/v), with UV detection at 243 nm for mixture 1, and mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 3 (50:50, v/v), with UV detection at 245 nm for mixture 2.The methods were validated in terms of accuracy, specificity, precision and linearity in the range of 20-60 microg ml(-1) for GU, 1-3 microg ml(-1) for SL, 20-80 microg ml(-1) for AC, 0.2-1.8 microgml(-1) for PP and 1-5 microg ml(-1) for BX and MP. The proposed methods were successfully applied for the determination of the two multicomponent combinations in laboratory prepared mixtures and commercial syrups. 相似文献
9.
Spectrophotometric and LC determination of two binary mixtures containing antihistamins 总被引:1,自引:0,他引:1
Several methods are developed for the determination of two binary mixtures containing cyclizine hydrochloride with pyridoxine HCl (mixture (mix.) 1); and cinnarizine with piracetam (mix. 2). The resolution of the two binary mixtures has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression applied to UV spectra of the mixture and graphical spectrophotometric method as second derivative of the ratio spectra (2DD). In addition, HPLC methods were developed depending on using RP18 column with mobile phase consisting of acetonitrile/0.05 M KH2PO4 (50:50, v/v, pH 4.0) with UV detection at 239 nm for mix. 1, and mobile phase consisting of acetonitrile/0.05 M KH2PO4/triethylamine (50:50:0.2, v/v/v, pH 3.0) with UV detection at 227 nm for mix. 2. The proposed methods were successfully applied for the determination of the two binary combinations in synthetic mixtures and commercial tablets. 相似文献
10.
Two different UV spectrophotometric methods were developed for the determination of rofecoxib in bulk form and in pharmaceutical formulations. The first method, an UV spectrophotometric procedure, was based on the linear relationship between the rofecoxib concentration and the lambdamax amplitude at 279 nm. The second one, the first derivative spectrophotometry, was based on the linear relationship between the rofecoxib concentration and the first derivative amplitude at 228, 256 and 308 nm. Calibration curves were linear in the concentration range using peak to zero 1.5-35.0 microg x ml(-1). HPLC was carried out at 225 nm with a partisil 5 ODS (3) column and a mobile phase constituted of acetonitrile and water (50 :50 v/v). A linear range was found to be 0.05-35.0 microg x ml(-1). The developed methods were successfully applied for the assay of pharmaceutical dosage form. The statistics of the analytical data is also presented. The results obtained by first derivative spectrophotometry were compared with HPLC and no significant difference was found. 相似文献
11.
In the present work, different spectrophotometric methods and one spectrofluorimetric method have been developed and validated for the determination of mosapride citrate in the presence of its acid-induced degradation products. The drug was subjected to stress stability study including acid, alkali, oxidative, photolytic, and thermal stress degradation. The developed spectrophotometric methods included the use of first order derivative ((1)D), derivative of ratio spectra ((1)DD), mean centring of ratio spectra (MC) and H-point standard additions (HPSAM) spectrophotometric methods. For (1)D method, the peaks amplitudes at 282.8 and 319.6 nm were measured, while for (1)DD method those at 308 nm and 323 nm were measured. Mean centring of ratio spectra method used the values at 317 nm for calibration, while for HPSAM the absorbance at 273 and 288.6 nm were used. These methods were successfully applied for determination of mosapride in the concentration range of 5-70 μg.ml(-1). The spectrofluorimetric method was based on measuring the native fluorescence of mosapride in 0.1 M NaOH using λ(excitation) 276 nm and λ(emission) 344 nm and 684 nm with linearity ranges of 50-3000 ng.ml(-1) and 50-9000 ng.ml(-1), respectively. All the developed methods were validated according to the International Conference on Harmonization (ICH) guidelines and were applied for bulk powder and dosage form. The results obtained were statistically compared to each other using one-way ANOVA testing. 相似文献
12.
Bhatia NM Ganbavale SK Bhatia MS More HN Kokil SU 《Indian journal of pharmaceutical sciences》2008,70(5):603-608
Rapid, precise, accurate, specific and sensitive reverse phase liquid chromatographic and absorbance ratio spectrophotometric methods have been developed for the simultaneous analysis of ambroxol hydrochloride and cetirizine hydrochloride in their tablet formulation. The chromatographic methods were standardized using a HIQ SIL-C(18) column (250×4.6 mm i.d., 10 μm particle size) with UV detection at 229 nm and mobile phase consisting of methanol-acetonitrile-water (40:40:20, v/v/v). Ambroxol hydrochloride and cetirizine hydrochloride have absorbance maxima at 243 nm and 229 nm, respectively. The isoabsorptive wavelength for both the drugs was 236 nm. For absorbance ratio method developed, wavelengths selected were 243 nm and 236 nm. The proposed methods were successfully applied to the determination of ambroxol hydrochloride and cetirizine hydrochloride in tablets, with high percentage of recovery, good accuracy and acceptable precision. Different analytical performance parameters such as linearity, precision, accuracy, limit of detection, limit of quantitation and robustness were determined according to International Conference on Harmonization ICH Q2B guidelines. Results of analysis of the developed method were compared by performing ANOVA. 相似文献
13.
Nikunj Rameshbhai Gohel Bhavin Kiritbhai Patel Vijaykumar Kunvarji Parmar 《Scientia pharmaceutica》2013,81(4):983-1001
Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241–290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3–30 μg/mL for TOL and 1–10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit. 相似文献
14.
El-Gindy A Ashour A Abdel-Fattah L Shabana MM 《Journal of pharmaceutical and biomedical analysis》2001,25(2):171-179
Two methods are described for the simultaneous determination of benazepril HCl and hydrochlorothiazide in binary mixture. The first method was based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 238 and 275 nm for benazepril HCl and hydrochlorothiazide, respectively. The separation was carried out on Merck HPTLC aluminum sheets of silica gel 60 F(254,) using ethyl acetate-methanol-chloroform (10:3:2 v/v) as mobile phase. Second order polynomial equation was used for the regression line in the range 2-20 and 2.5-25 microg/spot for benazepril HCl and hydrochlorothiazide, respectively. The second method was based on HPLC separation of the two drugs on reversed phase, ODS column at ambient temperature using a mobile phase consisting of acetonitrile and water (35:65 v/v) and adjusting to pH 3.3 with acetic acid. Quantitation was achieved with UV detection at 240 nm based on peak area with linear calibration curves at concentration ranges 10-60 and 12.5-75 microg ml(-1) for benazepril HCl and hydrochlorothiazide, respectively. The two proposed methods were successfully applied to the determination of both drugs in laboratory prepared mixtures and in commercial tablets. No chromatographic interference from the tablets excipients was found. 相似文献
15.
《Journal of pharmaceutical and biomedical analysis》1995,13(7):851-856
Two methods are described for the simultaneous determination of enalapril maleate and hydrochlorothiazide in combined pharmaceutical tablets. The first method depends on first-derivative ultraviolet spectrophotometry, with zero-crossing and peak-to-base measurement methods. The first-derivative amplitudes at 224 and 260 nm were selected for the assay of enalapril maleate and hydrochlorothiazide, respectively. The second method is based on high-performance liquid chromatography on a reversed-phase column using a mobile phase of acetonitrile-water (20:80, v/v) (pH 3.8) with programmable detection at 215 and 275 nm. Both methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and in commercial tablets. 相似文献
16.
Two new simple and selective assay methods have been presented for the binary mixtures of moexipril hydrochloride (MOEX) and hydrochlorothiazide (HCTZ) in pharmaceutical formulations. The first method depends on second-derivative ultraviolet spectrophotometry with zero-crossing measurements at 215 and 234 nm for MOEX and HCTZ, respectively. The assay was linear over the concentration ranges 1.0-11.0 microg ml(-1) for MOEX and 0.5-9.0 microg ml(-1) for HCTZ. The determination limits for MOEX and HCTZ were found to be 1.0 and 0.5 microg ml(-1), respectively; while the detection limits were 0.2 microg ml(-1) for MOEX and 0.1 microg ml(-1) for HCTZ. The second method was based on isocratic reversed-phase liquid chromatography by using a mobile phase acetonitrile-20 mM phosphate buffer (pH 4.0) (50:50, v/v). Lisinopril was used as an internal standard (IS) and the substances were detected at 212 nm. The linearity range for both drugs was 0.5-12.0 microg ml(-1). The determination and detection limits were found to be 0.100 and 0.010 microg ml(-1) for MOEX and 0.025 and 0.005 microg ml(-1) for HCTZ, respectively. The proposed methods were successfully applied to the determination of these drugs in synthetic mixtures and commercially available tablets with a high percentage recovery, good accuracy and precision. 相似文献
17.
Rapid, simple and accurate chromatographic (HPLC) method for the determination of trandolapril was elaborated. Samples were chromatographed on a LiChrosorb RP-18 column and the mobile phase was acetonitrile -0.067 M phosphate buffer pH 2.7 (7:3, v/v). The UV detection at 220 nm and benazepril as an internal standard were used. The method was tested for linearity (over the range 4-20 micrograms.ml-1), precision and accuracy and was successfully applied for the quantitative determination of trandolapril in capsules. 相似文献
18.
El-Sherif ZA El-Zeany B El-Houssini OM 《Journal of pharmaceutical and biomedical analysis》2005,36(5):975-981
Two reproducible stability indicating methods were developed for the determination of risperidone (RISP) in presence of its degradation products in pure form and in tablets. The first method was based on reversed phase high performance liquid chromatography (HPLC), on Lichrosorb RP C 18 column (250 mm i.d., 4 mm, 10 μm), using methanol:0.05 M potassium dihydrogen phosphate pH 7 (65:35 (v/v)) as the mobile phase at a flow rate of 1 ml min−1 at ambient temperature. Quantification was achieved with UV detection at 280 nm over a concentration range of 25–500 μg ml−1 with mean percentage recovery of 99.87 ± 1.049. The method retained its accuracy in the presence of up to 90% of RISP degradation products. The second method was based on TLC separation of RISP from its degradation products followed by densitometric measurement of the intact drug spot at 280 nm. The separation was carried out on aluminum sheet of silica gel 60F254 using acetonitrile:methanol:propanol:triethanolamine (8.5:1.2:0.6:0.2 (v/v/v/v)), as the mobile phase, over a concentration range of 2–10 μg per spot and mean percentage recovery of 100.1 ± 1.18. The two methods were simple, precise, sensitive and could be successfully applied for the determination of pure, laboratory prepared mixtures and tablets. The results obtained were compared with the manufacturer's method. 相似文献
19.
Nebsen M Abd El-Rahman MK Salem MY El-Kosasy AM El-Bardicy MG 《Drug testing and analysis》2011,3(4):221-227
Three sensitive, selective, and precise stability-indicating methods for the determination of the novel osteoarthritis drug, diacerein (DIA) in the presence of its alkaline degradation product (active metabolite, rhein) and in pharmaceutical formulation were developed and validated. The first method is a first derivative (D(1) ) spectrophotometric one, which allows the determination of DIA in the presence of its degradate at 322 nm (corresponding to zero crossing of the degradate) over a concentration range of 4-40 μg/mL with mean percentage recovery 100.21 ± 0.833. The second method is the first derivative of the ratio spectra (DD(1) ) by measuring the peak amplitude at 352 nm over the same concentration range as (D(1) ) spectrophotometric method, with mean percentage recovery 100.09 ± 0.912. The third method is a TLC-densitometric one, where DIA was separated from its degradate on silica gel plates using ethyl acetate:methanol:chloroform (8:1.5:0.5 v:v:v) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of DIA at 340 nm over a concentration range of 1-10 μg/spot, with mean percentage recovery 100.24 ± 1.412. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DIA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method. 相似文献
20.
Bebawy LI 《Journal of pharmaceutical and biomedical analysis》2002,27(5):737-746
Three methods are described for the simultaneous determination of dorzolamide hydrochloride (DORZ) and timolol maleate (TIM) in ophthalmic solutions. The first method is based on application of thin layer chromatographic separation of both drugs followed by the densitometric measurements of their spot areas. After separation on silica gel GF(254) plates, using methanol-ammonia 25% (100:1.5 v/v) as the mobile phase, the chromatographic zones corresponding to the spots were scanned at 253 and 297 nm, respectively. The calibration function was established in the ranges of 2-18 microg for DORZ and 0.5-4.5 microg for TIM. The second method depends on first derivative ultraviolet spectrophotometry, with zero-crossing measurement method. The first derivative values D(1) at 250.2 and 312.5 nm were selected for the assay of DORZ and TIM, respectively. Calibration graphs follow Beer's law in the range 10-64 and 2.5-16 microg ml(-1), respectively. The third method is based on ratio first derivative spectrophotometry. The signals in the first derivative of the ratio spectra at 244 and 306.2 nm were selected to determine DORZ and TIM in the mixture and calibration graphs are linear in the range of 5-40 and 5.0-17.5 microg ml(-1), respectively. The proposed methods were successfully applied to the determination of these compounds in synthetic mixtures and in pharmaceutical preparations. The proposed methods are simple, rapid and suitable for quality control application. 相似文献